Evolution of ACE2 and SARS-CoV-2 Interplay Across 247 Vertebrates

  1. Tao Zhang
  2. Qunfu Wu
  3. Yicheng Ma
  4. Wenjing Liu
  5. Chengang Zhou
  6. Zhigang Zhang

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause the most serious pandemics of Coronavirus Disease 2019 (COVID-19), which threatens human health and public safety. SARS-CoV-2 spike (S) protein uses angiotensin-converting enzyme 2 (ACE2) as recognized receptor for its entry into host cell that contributes to the infection of SARS-CoV-2 to hosts. Using computational modeling approach, this study resolved the evolutionary pattern of bonding affinity of ACE2 in 247 jawed vertebrates to the spike (S) protein of SARS-CoV-2. First, high-or-low binding affinity phenotype divergence of ACE2 to the S protein of SARS-CoV-2 has appeared in two ancient species of jawed vertebrates, Scyliorhinus torazame (low-affinity, Chondrichthyes) and Latimeria chalumnae (high-affinity, Coelacanthimorpha). Second, multiple independent affinity divergence events recur in fishes, amphibians-reptiles, birds, and mammals. Third, high affinity phenotypes go up in mammals, possibly implying the rapid expansion of mammals might accelerate the evolution of coronaviruses. Fourth, we found natural mutations at eight amino acid sites of ACE2 can determine most of phenotype divergences of bonding affinity in 247 vertebrates and resolved their related structural basis. Moreover, we also identified high-affinity or low-affinity-associated concomitant mutation group.The group linked to extremely high affinity may provide novel potentials for the development of human recombinant soluble ACE2 (hrsACE2) in treating patients with COVID-19 or for constructing genetically modified SARS-CoV-2 infection models promoting vaccines studies. These findings would offer potential benefits for the treatment and prevention of SARS-CoV-2.

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  1. ScreenIT

    SciScore for 10.1101/2021.01.28.428568: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Obtaining amino acid sequences of ACE2 and the S protein of SARS-CoV-2: Raw ACE2 amino acid (AA) sequences belonging to vertebrates were downloaded from the nr database from NCBI and UniProt database.
    UniProt
    suggested: (UniProtKB, RRID:SCR_004426)
    The ACE2 protein tree of 247 vertebrates was built using MEGA X[48] and annotated with Interactive Tree Of Life (iTOL) v 5.51[49].
    MEGA
    suggested: (Mega BLAST, RRID:SCR_011920)
    Corresponding to hACE2, we extracted from contact 22 amino acid residues from 247 vertebrates’ ACE2 based on the Mega X aligned file using BioEdit v7.2.5.
    BioEdit
    suggested: (BioEdit, RRID:SCR_007361)
    The Structures alteration for MT hACE2 mutated by functional AA changes relative to WT hACE2: The 3D Complex Structure presentation was performed using PyMOL v2.0[52] with pdb file generated from protein structure homology modeling with SWISS-modeling workspace in automated mode (Figure 4).
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2021.01.28.428568v1 on bioRxiv